Renin as a Marker of Tissue Perfusion, Septic Shock and Mortality in Septic Patients: A Prospective Observational Study

Abstract

Sepsis is a life-threatening organ dysfunction caused by the dysregulation of the host’s response to an infection, where the dominant mechanism is tissue hypoperfusion. Currently, the marker used to define tissue disorders is lactate levels, which may be elevated in other disease states as well. Renin is an essential hormone for the proper functioning of the renin-angiotensin-aldosterone (RASS) system. It is secreted in the glomerular apparatus in response to hypoperfusion. This study aimed to assess the usefulness of renin as a marker of tissue hypoperfusion in patients with sepsis and septic shock. A final group of 48 patients treated for sepsis and septic shock in the intensive care unit was included. Blood samples for renin quantification were collected in the morning as a part of routine blood analysis on the first, third, and fifth days. Sepsis was diagnosed in 19 patients (39.6%), and septic shock was diagnosed in 29 patients (60.4%). There was no significant difference in renin concentration between patients who received and did not receive continuous renal replacement therapy (CRRT) on any study day. Therefore, all samples were analyzed together in subsequent analyses. There was a significant difference in renin concentration between sepsis survivors and non-survivors on the third (31.5 and 119.9 pg/mL, respectively) and fifth (18.2 and 106.7 pg/mL, respectively) days. As a survival marker, renin was characterized by 69% and 71% overall accuracy if determined on the third and fifth days, respectively. There was a significant difference in renin concentration between sepsis and septic shock patients on the first (45.8 and 103.4 pg/mL, respectively) and third (24.7 and 102.1 pg/mL, respectively) days. At an optimal cut-off of 87 pg/mL, renin had very good specificity and a positive likelihood ratio. Renin was a strong predictor of mortality in patients with sepsis and septic shock. Further, the level of renin in patients with septic shock was significantly higher than in patients with sepsis. In combination with the assessment of lactate concentration, renin seems to be the optimal parameter for monitoring tissue hypoperfusion and could be helpful for septic shock diagnosis, as well as for identifying candidate patients for CRRT.

Renin as a Prognostic Marker in Intensive Care and Perioperative Settings: A Scoping Review

“…Our search strategy identified a total of 2081 records. After screening, we included 16 studies with 1573 critically ill or perioperative patients (Figure) 6,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] with major exclusions and reasons for exclusion detailed in Supplemental Digital Content 1, Supplemental Table 1, http://links.lww.com/ AA/E504. Except for 2 studies, 16,21 the other 14 were published after 2017.…”

“…Except for 2 studies, 16,21 the other 14 were published after 2017. Shock (mainly vasodilatory or septic shock) was the most common etiology 11,12,15,18,20,21,23 and most of the included articles were prospective observational studies. 6,[12][13][14][15][16][17][18][20][21][22]24,25 The characteristics of the included studies are summarized in Table 1.…”

“…Most studies (14, 88%) measured serum renin levels by concentration, 6,11,[13][14][15][17][18][19][20][21][22][23][24][25] while only 2 studies evaluated renin activity. 12,16 The measured renin values were different between studies even though the method and unit of measurement was the same.…”

Renin as a Prognostic and Predictive Biomarker in Sepsis: More Questions Than Answers?*

“…Recently, renin has been proposed as a candidate biomarker in sepsis. Several post hoc and secondary analyses of randomized controlled trials, as well as observational studies, have reported associations between renin level or renin kinetics and sepsis outcomes (2–5). Renin is an upstream effector of the renin–angiotensin system (RAS) that converts angiotensinogen to angiotensin I, which is then converted to angiotensin II by the angiotensin-converting enzyme (ACE).…”

“…A modest but growing number of studies suggest that renin may hold promise as a prognostic and predictive biomarker. Several studies have reported an association between elevated renin levels and adverse clinical outcomes, including mortality (2, 4, 5) or acute kidney injury (3, 5), in patients with sepsis. Some studies have suggested that renin levels may be more sensitive and specific than arterial lactate in predicting mortality (10).…”